This is a Program Project Application for three years of support to establish a Center for the Study of Neurodegenerative Diseases at the University of Virginia. The Program will be directed by James P. Bennett, Jr., M.D., Ph.D. and will be based in the Department of Neurology. The application is composed of five individual projects and two cores, has a broad scientific base, and has arisen from the evolving collaborative efforts over time of the investigators. Four neurologist and one neurosurgeon clinician-investigators and four basic neuroscientists will pursue projects that will characterize the control of neurotrophic factor metabolism, potential transsynaptic and neuroimmunological etiologies of neurodegenerative diseases (NDD), neuroplastic adaptations in animal models of human NDD, and the biological basis for improved pharmacologic and transplantation therapies of NDD. All projects will be supported by an administration core and a Molecular and Cellular Anatomy core laboratory. Synergistic interactions among the investigators will be encouraged by quarterly meetings and regular annual review by outside consultants.